The present invention relates to a water soluble adduct (as herein defined) of 1-ethyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylic acid (hereinafter called "Norfloxacin").
Adduct in connection with the present invention means an adduct proper, a salt (including addition salt), a complex etc.
Norfloxacin, which is described and claimed in U.S. Pat. Nos. 4,146,719 and 4,292,314, is a very effective antibacterial agent having a broad spectrum of activity. However, it has a very low water solubility at the normally used pH range, i.e. 6-10.
In many cases it is advantageous to apply a medicament by way of injections, solutions, infusions, etc. Moreover, it is well known that when livestock or fowl are ill the medicament is advantageously administered in the drinking water. As the result of its low water solubility the use of Norfloxacin in the above indicated manner is rather restricted or even impossible.
Certain Norfloxacin salts are known, inter alia, from the following publications:
U.S. Pat. No. 4,530,928 describes and claims a complex of Norfloxacin with guanidium carbonate. However, the solubility of said complex in water is also rather low.
Israeli Pat. No. 66,026 describes and claims the galacturonic, aspartic, glutamic and gluconic salts of Norfloxacin. The solubility of said salts in water is much better. However the preparation of said salts is by way of lyophilization and is expensive.
The above Israeli patent also describes other salts of Norfloxacin. However, it is explicitly stated that these other salts cannot be used for parenteral purposes, i.e. some of them are not sufficiently water-soluble in the required pH range; some are difficult to manufacture by lyophilization (acetate) or the acid part cannot be consistently obtained in a satisfactory grade (lactate).
From DE Pat. No. 3,333,719, a water-soluble composition comprising the lactate of Norfloxacin together with a further acid which does not cause any precipitation is known. This composition is also not satisfactory, not only for the reasons given above, but also because it requires the use of a further acid which complicates the preparation thereof.
It has thus been desirable to find a water-soluble Norfloxacin derivative which overcomes the above drawbacks. Said derivative should, inter alia, be suitable in the veterinary field, e.g. in the treatment of fowl. It should be relatively inexpensive and easy to manufacture, be biostable on being dissolved in water and have a high solubility so that a commercially feasible water concentration can be prepared which can be, if desired, further diluted. Moreover, said derivative should, after having been administered internally, ensure an adequate blood level.
Adducts of nicotinic acid with related acids, e.g. that of Enoxacin and of Pefloxacin were prepared. However, these adducts have a very low solubility in water.